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New optical methods for investigating the activity of small molecules in cells may facilitate development of anticancer therapeutics. Here, the authors use a super-resolution optical platform and single molecule tracking to gain insight into WRN regulation in cancer.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Chromosomal rearrangements are key events in the pathogenesis of a range of disorders. Here the authors utilize a zinc finger nuclease translocation reporter to identify PARP3 as a regulator of these events at sites enriched for G quadruplex DNA.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Cultured archaeal viruses, which so far all have double-stranded DNA genomes, come in all shapes and sizes, with the range of virion morphotypes surpassing that found in the viruses of the Bacteria. The authors present a unifying view of this fascinating viral group.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Kavlashvili et al. use a new in vitro approach to show that uncoupled replication forks can cause fork reversal and nascent strand degradation. Both processes occur without loss of the replisome from DNA and degradation involves multiple steps.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Sister chromatid exchanges (SCEs) are considered to be products of homologous recombination repair. The authors show that SCEs can arise independently of homologous recombination due to processing of replication intermediates during mitosis.

Daniel Benjamin, Meike Bartels, Philipp Koellinger and colleagues report a genome-wide association meta-analysis of subjective well-being, depressive symptoms and neuroticism. The study leverages a large sample size together with genetic correlations between the phenotypes to identify, with high confidence, loci associated with each phenotype.

Ribosomal DNA repeats are essential for maintaining genome integrity.

The CENP-A chaperone HJURP associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. Here the authors provide evidence that two repeats in human HJURP previously proposed to be functionally distinct are interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it.

The endonuclease XPF-ERCC1 is a key component of the repair machinery to process both intra-strand and inter-strand DNA crosslinks. Here the authors present the cryo-EM structures of DNA-free and DNA-bound human XPF-ERCC1 and find that DNA-free XPF-ERCC1 adopts an auto-inhibited conformation, which is opened up upon DNA binding and they also characterise the biochemical properties of patient-derived XPF-ERCC1 mutations.

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.

This article describes the important advances in our understanding of recombination in humans and mice, from the properties and activity of individual hot spots to the control of the recombination landscape along chromosomes and between the sexes.

Aaron Gitler, Robert Farese Jr. and colleagues identify the RNA lariat debranching enzyme Dbr1 as a potent suppressor of TDP-43 toxicity in yeast. They further show that Dbr1 knockdown reduces TDP-43 toxicity in mammalian cells, identifying this enzyme as a possible therapeutic target in amyotrophic lateral sclerosis and other diseases marked by TDP-43 accumulation.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

In-depth morphological and molecular analyses of two haptophyte-infecting viruses reveal intricate virus-host interactions and a viral origin of chromosome proteins of dinoflagellates.

Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. Here, the authors provide evidence that these hypersensitivities reflect a crucial role for ATM at damaged replication forks being to prevent toxic DNA end-joining leading to chromosome fusions and cell death.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

Classical Hodgkin lymphoma is a cancer that originates in lymph nodes. Little is known about its genetic susceptibility. Here, the authors combined existing and new genome-wide association studies to identify risk loci for classical Hodgkin lymphoma at 6q22.33, and nodular sclerosis Hodgkin lymphoma at 3q28, 6q23.3, 10p14, 13q34, 16p13.13.

Genome-wide association analysis of irritable bowel syndrome identifies genetic susceptibility loci and highlights shared pathways with mood and anxiety disorders.

Wind stress controls annual variations in the Atlantic meridional overturning circulation at mid-latitudes, while surface buoyancy also matters at subpolar latitudes, according to an attribution analysis using a numerical model constrained by observational array data.

Anna Köttgen and colleagues report genome-wide association studies for serum urate in over 140,000 individuals from the Global Urate Genetics Consortium (GUGC). They identify 18 loci newly associated with serum urate concentrations and confirm 10 known loci, characterize their associations with gout and include a network analysis suggesting a role for inhibins-activins pathways in regulating urate homeostasis.

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.

Transcription termination or pausing during DNA replication in bacteria and humans results in DNA damage with exposed 3′ single-stranded DNA ends and mutations.

A genome-wide association study in 293,723 individuals identifies 74 genetic variants associated with educational attainment, which, although only explaining a small proportion of the variation in educational attainment, highlights candidate genes and pathways for further study.

Although the tuberculosis bacterium is most renowned for its ability to cause pulmonary infection, the bacilli colonize many sites in the body in addition to the lungs. The recent identification of a key player in the dissemination of infection sheds light on the route by which tuberculosis spreads from the lungs and opens the way to assessing the significance of dissemination to the course of disease.

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

Pulmonary function is influenced by environmental factors, lifestyle, and genetics. Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry.